Pharmaceutical validation is a systematic process that ensures

pharmaceutical products are consistently produced to meet

quality standards. It is a vital part of the pharmaceutical industry,
where safety and precision are paramount.
The process of establishing documentary evidence
demonstrating that a procedure, process, or activity carried out in
testing and then production maintains the desired level of
compliance at all stages.
What is validation?
Validation is a process of establishing documentary evidence
demonstrating that a procedure, process, or activity carried out in
production or testing maintains the desired level of compliance at
all stages. In Pharma Industry it is very important apart from final
testing and compliance of product with standard that the process
adapted to produce itself must assure that process will
consistently produce the expected results. Here the desired
results are established in terms of specifications for out come of
the process. Qualification of systems and equipment is therefore
a part of process of validation. It is a requirement of food and
drug, pharmaceutical regulating agencies like FDA's good
manufacturing practices guidelines. Since a wide variety of
procedures, processes, and activities need to be validated, the
field of validation is divided into a number of subsections
including the following:
• Equipment validation
• Facilities validation
• HVAC system validation
• Cleaning validation
• Process Validation
• Analytical method validation
• Computer system validation
• Packaging validation
What is 21 CFR Part 11 and EU Annex 11?
• 21 CFR (Code of Federal Regulations) Part 11 has defined by
the US FDA regulations that set forth the criteria applies to
electronic records and electronic signatures that persons
create, modify, maintain, archive, retrieve, or transmit under
any records or signature requirement set forth in the Federal
Food, Drug, and Cosmetic Act, the Public Health Service
Act, or any FDA regulation
• Annex 11 is part of the European GMP Guidelines and
defines the terms of reference for computerized systems
software used by organizations in the pharmaceutical
industry.

GAMP 5, released in 2008, introduced significant improvements

over GAMP 4. The key difference lies in the approach: GAMP 4
focused more on procedural and documentation aspects, while
GAMP 5 emphasizes a risk-based approach
Any relation between GAMP 5 or v Model with 21 CFR Part 11?
• Both are the set of guidelines which are used to validate a
computer-based software used in pharma manufacturing
companies.
• The guidelines are predefined, and software should comply
with the guidelines.
• GAMP talks about “the How” and the 21 CFR talks “the
What” during the Validation of computer-based software for
Pharma companies.
• GAMP is a methodology and 21 CFR are a regulation
• 21 CFR Part 11 is US FDA and Annex 11 is EU guidelines.
GAMP 5 is an updated version of GAMP 4 that emphasizes risk-
based approaches and is more flexible and efficient for validating
computerized systems:
• Approach
GAMP 5 takes a risk-based approach, while GAMP 4 is more
traditional and procedural. GAMP 5 also focuses on scalability
and flexibility to adapt to different system complexities.
• Software categories
GAMP 5 modifies the software categories to better reflect risk to
quality and data integrity. GAMP 5 also removes the firmware
category.
• Compatibility
GAMP 5 is designed to be compatible with many international
standards.
 • Regulatory guidance
GAMP 5 incorporates the latest regulatory guidance from
organizations like the FDA and ICH.
• Technology
GAMP 5 has been updated to include current technology like
artificial intelligence (AI), machine learning (ML), and blockchain.
Design qualification (DQ) - Demonstrates that the proposed
design (or the existing design for an off-the-shelf item) will satisfy
all the requirements that are defined and detailed in the User
Requirements Specification (URS). Satisfactory execution of the
DQ is a mandatory requirement before construction (or
procurement) of the new design can be authorised.
Installation qualification (IQ) – Demonstrates that the process
or equipment meets all specifications, is installed correctly, and
all required components and documentation needed for
continued operation are installed and in place.
Operational qualification (OQ) – Demonstrates that all facets of
the process or equipment are operating correctly.
Performance qualification (PQ) – Demonstrates that the process
or equipment performs as intended in a consistent manner over
time.
Operational qualification is the next step in quality assurance and
involves testing the equipment and making sure it performs as
specified, within operating ranges as listed by the manufacturer.
within the accepted range as specified, does it perform as
expected under real conditions.
 • User Requirement Specification (URS)
The URS is a definition of requirements to fulfil the demands of
the process from the Users' point of view. The success of a GMP
cleanroom design is dependent on a clear and concise User
Requirement Specification (URS) to take through a successful
Design Qualification

• functional specification
A functional specification is a formal document used to describe
a product's intended capabilities, appearance and interactions
with users in detail for software developers. The functional
specification is a kind of guideline and continuing reference point
as the developers write the programming code.
• Project Specific Quality Plan (PSQP)
he PSQP describes:
• Quality activities to be carried out during the project
• Key people in Siemens and customer responsible for the
quality activities
• Sequencing of quality activities and their prerequisites
• Project instructions and guidelines for the quality activities
The PSQP is a living document and will be updated as necessary
during project implementation. Any changes will cause the entire
plan to be revised and re-issued.
 • Configuration Specification (CS) – PX

This document, in conjunction with the Functional

Specification (FS) and the Software Design Specification
(SDS), describes how the customer's requirements from the
User Requirements Specification (URS) are met. This
Configuration Specification (CS) was developed based on
the FS.

The CS is a living document which maintains the status

"Validated", therefore the change procedure must be
followed.

• Configuration Specification (CS) - ML DCC

In conjunction with the Functional Specification (FS), this
document describes how the customer's requirements from the
User Requirements Specification (URS) are met. This
configuration specification (CS) was developed based on the FS.
The CS is a living document with which the status is "Validated",
therefore the amendment procedure must be followed.An "As-
Built" management level document, specifying the current
configuration, is prepared after the design phase, on-site
installation and prior to the SAT. To do this, the version of the CS-
ML is raised to the status "As Built" and the document version is
increased.
The "As-Built" version is used in the SAT and IQ / OQ / IOQ tests to
verify configurations.
 • Factory Acceptance Test (FAT) – PX
The Factory Acceptance Test (FAT) is carried out according to this
specification to verify compliance with URS requirements before
the system is delivered to customer sites.
The FAT is used to check the proper functioning of hardware and
software in accordance with the FS and the CS, so that deviations
can be identified and corrected at an early stage.

• Factory Acceptance Test (FAT) - Desigo CC

The Factory Acceptance Test (FAT) is performed according to this
specification to verify compliance with the URS requirements
before the system is shipped to the customer's site.
The FAT is used to check the proper functioning of hardware and
software in accordance with the FS and the CS, so that deviations
can be identified and corrected at an early stage.
• Site Acceptance Test (SAT)
The SAT verifies that the installed hardware and software operates
correctly in the EMS network and that there are no conflicts or
network problems. Hence, the SAT confirms firstly that the
settings are correct and secondly that the interaction between
hardware and software are as required.
The hardware and software configuration are verified against the
design specification.
The test specification describes the test and defines the
acceptance criteria, documentation and reference literature
necessary to ensure that the hardware and software are
implemented in accordance with GAMP 5, the GAMP Good
Practice Guide for the testing of GxP systems and customer
procedures and the URS requirements.
SAT will be performed separately for:
Rooms and areas
A SAT report will be issued when all tests are completed.
 • FAT Report
The FAT report confirms that the specifications have been met
and provides documented evidence of the completion of the FAT.
The specification means the correctness of the configuration of
software and hardware
• SAT Report
The SAT report confirms that specifications have been met and
serves as proof of completion of the SAT. Specification means the
correctness of the installation of software and hardware.
The traceability refers to the life cycle documentation (URS to FAT
/ SAT). The IQ / OQ or IOQ documents are not listed in the TM
because these documents refer to the FAT and SAT!
 • Risk Classification (RC)

This risk classification (RC) evaluates the risks associated with

the customer devices or the customer system and reduces any
GMP-critical risks through well-defined measures.

• FMEA

This document describes the method, responsibilities and results

of the risk analysis (FMEA) performed based on the requirements
of the user requirements listed in the reference documents
section.
 • Traceability Matrix
This traceability matrix ensures that all requirements from the
User Requirement Specification (URS) are implemented in the
design documentation of Siemens. At the same time, it is ensured
that the requirements are verified via test specifications.
 • Environmental Monitoring System
Environmental Monitoring is critical in the regulated industries for
ensuring compliance and product safety. By leveraging advanced
functionalities like integrating existing systems, real-time
monitoring, and easy tracking, businesses can optimize
operations efficiently. Ensuring strict compliance and ensure
product integrity using advanced sensors and analytics.
• Automated monitoring
Excellent monitoring of the environment for microbial checks
• Regulatory Compliance
Meet regulatory standards like US FDA 21 CFR Part 11, EU
Annexure 11, etc
• Auto Alert System
Real-time alerts for exceeding predefined limits, adherence to
sampling frequency and locations specified in SOPs
• Easy Tracking
Improved tracking of contamination sources and their addressal

GAMP 5 GAMP-4
PSQP 1
FS 1 Design Qualification (DQ)
FAT 1 Installation Qualification (IQ
SAT 1 Operation qualification (OQ)
Performance qualification
IQ
1 (PQ)
RA 1
DQ 1
BMS Inputs
1. Drawings (Electrical, Schematic, ..)
2. Design Specifications
3. HDS (Hardware specifications)
4. FDS (Software specifications)
5. Functional specifications
6. Instrument test certificates
7. I/O List
8. Boundary Limits
9. Alarm’s
10. P&ID
EMS Inputs
1. Design specification
2. HDS (Hard ware specifications)
3. FDS (Software specifications)
4. Functional specifications
5. Drawing
6. Alarm’s
7. Boundary limits
8. Instruments test certificates

URS Input Requirement

Field Sensors Type:

Field Sensors Range:
Local Indicators:
Particle Counter:
Operating Manuals:
Controller Future Expansion (%)
IO Spare Capacity (%)
Operating Workstation Spec
Printer
Date & Time Format
Reundancy Type & Details
Desigo CC User Group

PSQP Input Requirement

System Topology
Customer URS
Project Team Structure
Project Team Responsibilities
Desigo CC Product Version:
Desigo CC Platform built:
Windows Server Version:
SQL Server Version
Validation document standard:
Sub-Supplier
FS

Control Panel, Hardware and types

Control Panel Labelling
Internal Enclosure temperature
Ambient temperature
Ambient humidity
Trend for Temperature
Trend for Humidity
Trend for Particle Count
Trend for Differential Pressure

FS Input Requirement

Control Panel, Hardware and types

Control Panle Labeling
Internal Enclosure temperature
Ambient temperature
Ambient humidity
Trend for Temperature
Trend for Humidity
Trend for Particle Count
Trend for Differential Pressure

CMP - ML DCC Input Requirement

Server Configuration
Configuration of the VM
Configuration of Monitor
Configuration of Keyboard
Configuration of Mouse
Configuration of Event Printer
Configuration of Alarm Printer
Configuration of UPS
Network Configuration
Installed Software
License of the Installed Software
Day Light Saving Configuration
Remote access configuration (cRSP)
SMC-System
SMC-Projects
SMC-Websites
SMC-Certificates
Address book
Documents
Definition of Macros
Reactions
RENO Notifications
Reports
Schedules
Trends
Field Networks
Management System
Operation Modes
Assisted Treatment
Configuration of Users
User Groups (Security)
Scopes
SQL Server Configuration
Hardware configuration details
Software configuration detail
Software List
Web clients
Configuration of Distributed
Network
UPS Software configuration

FAT - ML DCC Input Requirement

Verification of design documents

Verification of Server Hardware / VM
Verification of Server related
components
Verification of Installed Software
Verification of Operating System
Verification of Desigo CC

SAT Input Requirement

Version Verification of the EMS/BMS design documents

Version Verification of the software installed
Version Verification of the controller application
Verification of the accuracy of the delivered sensors
Verification of the calibration of each critical sensor
Verification of the loop calibration
Verification of the ambient conditions
Verification of the start-up of the complete Panel hardware after
power failure
Verification of the standalone functionality of the automation
station

• Design Qualification
Windows operating system
• General requirements
• Time synchronization
• User administration
GAMP-4
Installation Qualification Operational Qualification
BMS Graphics User interface (GUI)
• GUI version
• Support for Validated Environments
• Trend Viewer
• Reports
• Audit trail
• Alarms and monitoring
• System access, User rights and
configuration
• Backup
• Archiving
• Connectivity
Hardware
• Server
• Automaton Level
• Trend, trend data
• Data management
• Field Devices
• Network
• Ambient conditions
• Power supply
• Physical identification (labeling)
Documentation
• Design Documents
• Drawings
• Validation Documentation
• Technical documentation
• SOP
• Installation Qualification
• DDC Panel and Its Internal Components Verification
• • Prerequisites
• • Required Calibrated Tools
• • Reference Documents
• • DDC Panel And Its Internal Components Verification
• Field Devices Verification
• • Prerequisites
• • Required Calibrated Tools
• • Reference Documents
• • Field Devices Verification Procedure
• Drawings Verification
• • Prerequisites
• • Reference Documents
• • DDC Panel And Its Internal Components Verification
• Hardware Components installation Verificatio
• DESIGO PX automation level
• • Calibration list – test equipment
• • Test description – Verification of the technical
 • documentation
• Software details verification
•

• Operational Qualification
Calibration Verification
• Prerequisites
• Required Calibrated Tools
• Reference Documents
• Calibration Verification
• Device Calibration Verification Form
• Test Instruments Calibration Verification Form
Io’s Verification
• Prerequisites
• Required Calibrated Tools
• Reference Documents
• Io’s Verification Form Verification Procedure
• Io’s Verification Form
Alarm Verification
• Prerequisites
• Required Calibrated Tools
• Reference Documents
• Alarm Verification Procedure
• Alarm Verification Form
DDC Communication And Power Failure
Recovery Verification
• Prerequisites
• Required Calibrated Tools
• Reference Documents
• DDC Communication And Power Failure
• Recovery Verification
• DDC Communication and Power Failure
• Recovery Verification Form

• URS
1. Time synchronization
2. Events/Alarms
3. Security & Audit trail
4. Access Control
5. Data Management
6. Data acquisition
7. HMI visualization & report
8. Power requirements
9. Hardware identification & Environment Condition
10. Instrument Requirements
11. Requirements on documentation
- Design documentation
-Technical Document
- Trainings
 • PSQP
1. Siemens Smart Infrastructure Quality system
2. Project language
3. Document number
4. Siemens Document Cycle
5. Specification
- Design Specification
- Test Specification
-Siemens Standard Test content
6. Reports
7. Non conformités
8. Document Management
9. Change control
10. Project responsibilities
11. Project Team structure
12. Project structure Plan PSP
13. Project Approval
• FS
1. Field level
-Sensors & particle counter
2. Automation Level
-Desigo PX
-Version Control
-Data Management
-Hardware specs
-Functions: alarms, trends, time synchronization
3. Management level
-Hardware
-Windows OS
*User Admin
*Version control
*Backup/Archive
*Time synchronization
-Monitoring & event Handling- Desigo CC
• CMP-PX
1. Hardware CI list
2. Sensors
3. Controllers
4. Application Program
5. Control Cabinet
• CMP-ML DCC
Desigo cc Server
-Hardware Configuration
-Network Configuration
-Software list
-Licenses
-OS
-CRSP
-SQL Server SMC
-IISDsitributed
-Desigo cc SMC
- Networks
2. Desigo cc Project
-Management View
-Application View
-Logical View
-Report view
3. Desigo cc Clients
-Installed Clients
-Web Clients
-Verification of the general
fault control.
• FAT-PX
2. DDC Controller
-Verification of correct
controller network setting.
-Verification of the memory
usage
-Verification of the
application program
3. Documents-Version verification of the design documents
• FAT-CC
1. Server Hardware
-Verification of server hardware /
Verification of VM requirements
-Verification of server-related components
2. Server software
-Version verification of the installed
software
-Verification of the operating system
settings
-Verification of Desigo CC settings
3. Documents
-Version verification of the design
documents- FS & CMP CC
• SAT-PX
Loop Test
-Verification of the accuracy of the delivered
sensors
-Verification of the calibration for each critical
sensor
-Verification of the loop calibration
2. Verification of the Infrastructure environment
and power failure
-Verification of the ambient conditions
-Verification of the standalone functionality
-Verification of the backup battery
-Verification of the start-up of the complete
control cabinet hardware after power failure.

• SAT-CC
Verification of the server and related hardware
-Verification of the printer
-Verification of the UPS hardware
-Verification of the startup of the Server after power
failure
-Verification of the server location
2. Functional verification of the server OS
-Functional verification of user activity after period of
inactivity
-Functional verification of the network printer
3. Verification of the IIS configuration
4. Verification of the Long-Term Storage
5. Verification of the System Management Console
6. Functional verification of the Desigo CC project and HDB
backup
7. Verification of the server software
8. Verification / Functional Verification of the installed
Desigo CC Client, Web Client or Windows App Client
9. Verification of the Desigo CC HMI
10. Functional verification of Desigo CC alarm handling
11. Verification of validated objects
12. Functional verification of the Audit Trail in Desigo CC
13. Functional verification of trending in Desigo CC
14. Verification of Advanced (Pharma) Reports
15. Training
16. Technical documentation
17. Performance testing
18. Functional verification of the Desigo CC maintenance,
auto-shutdown function
19. Test description – VPN
• FAT-Report
1. Test Results
2. Report
3. Deviation/Discrepancies
• RC on URS
1. Product quality
2. Impact on process reproducibility
3. Cleaning or sterilizing
4. Contamination impact
5. Documentation including quality records
and critical process data

• FMEA
1. Failure, Effect & Detection mode
2. Risk Priority number
3. Measures
4. Repeat Failure, Effect & Detection mode